Evidence exists that cholecystokinin (CCK) is an important mediator in the feedback control of pancreatic secretion (J Lab Clin Med 105:1590;1985). Consistent with this, elevated plasma CCK levels have been documented in painful chronic pancreatitis (CP). We hypothesized that an obstructed pancreatic duct might cause elevated plasma CCK levels and that decompressing an obstructed duct would increase delivery of pancreatic enzymes to the intestine, and in turn, suppress CCK secretion. If so, CCK levels may serve as a non-invasive marker of successful duct decompression and pain relief. Seventeen patients with CP referred for possible endoscopic pancreatic duct (PD) stenting had baseline levels of plasma CCK measured and completed a Likert pain scale. 11 underwent stent placement. Prior to stent extraction, these patients had repeat CCK levels drawn and completed a second pain scale. Mean pre-treatment CCK levels in all patients was 2.54 pM which decreased post-treatment to 1.52 pM (P=0.11). Pain decreased in 7 patients, did not change in 1, and worsened in 3. The 7 patients describing pain relief had a 47% decrease in CCK levels (-20% to 68% range, p=0.24). The 3 patients with increased pain had a nonsignificant trend toward increased CCK levels. The mean pre-treatment level of CCK in patients who improved was 3.49 pmol/l as compared to 0.86 pmol/l in patients who remained the same or deteriorated (p=0.05). These preliminary results suggest that patients who experience pain relief after endoscopic stenting of the pancreatic duct have (1) higher fasting CCK levels, and (2) a decrease in CCK levels with stenting than those patients who do not experience pain relief. Fasting plasma CCK levels may have a role in identifying patients with chronic pancreatitis and pancreatic duct strictures who may benefit from a trial of endoscopic therapy, and may also be a non-invasive marker of PD decompression efficacy. Further evaluation is needed to confirm these early results.